Metformin, as an oral hypoglycemic agent of the biguanide class, still maintains its position as the first-line treatment for Type 2 diabetes, despite 60 years of clinical use. Although the drug’s glucose-lowering effect is primarily attributed to reducing glucose production in the liver, its precise mechanisms of action are not fully understood.
In addition to glycemic control, metformin is associated with extra benefits, such as anti-inflammatory, anti-cancer, anti-atherosclerosis, and anti-obesity effects.
According to one hypothesis, the additional beneficial effects of metformin may be explained by its ability to bind (chelate) metal ions in the body. This means that the drug can form chemical bonds with metals, thereby altering their biological activity and level.
Studies conducted under laboratory conditions have confirmed that metformin can form complex compounds (chelates) with metals, especially copper. According to a theoretical assumption, this binding may affect the cell’s energy-generating system (mitochondrial function) and intracellular communication processes (cellular signaling). Nevertheless, until now, it was unknown whether this chemical interaction actually occurs in the bodies of people with diabetes.
It is a known fact that changes in the levels of copper, iron, and zinc in the body are linked to diabetes and its complications. Specifically, an excess of copper and iron in the blood often indicates impaired glucose control and a high risk of cardiovascular diseases. In contrast, zinc is considered beneficial because it helps with glucose metabolism and reduces the likelihood of complications.
A new study, published in the journal BMJ Open Diabetes Research & Care, aimed to determine whether metformin affects blood metal levels. The study was conducted on 189 adults with Type 2 diabetes. Of these, 93 participants had been taking metformin for at least 6 months, while the remaining 96 were not.
According to the study results, the following correlations were found:
Patients taking metformin had significantly lower copper concentrations compared to non-users, and a decrease in iron concentration was also noted in this group, which was confirmed by the analysis of ferritin and other relevant markers. Furthermore, zinc levels were higher in metformin users.
According to the study results, the reduction of copper and iron in the blood, along with the increase in zinc, may be the mechanism that underlies the drug’s glucose-lowering and protective effects against diabetic complications. This finding is consistent with earlier studies in which a reduction in copper improved cell function (mitochondria), reduced inflammation, and slowed tumor growth.
The scientists believe that further clinical and animal studies are necessary to establish the exact cause-and-effect relationship between metformin’s action and its benefits.
